Department of Endocrinology, Post Graduate Institute of Medical Research and Education, Chandigarh, India.
Stem Cells Dev. 2009 Dec;18(10):1407-16. doi: 10.1089/scd.2009.0164.
Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and beta-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (> or = 0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by > or = 50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement (r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group (P = 0.03) and responders (P = 0.03). HOMA-B increased significantly in the whole group (P = 0.02) and responders (P = 0.04) whereas, HOMA-IR did not change significantly (P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline (r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells (r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.
进行性和不可逆转的β细胞功能障碍是 2 型糖尿病（T2DM）的标志，使用干细胞治疗进行β细胞再生可能被证明是一种有效的方法。共纳入 10 例 T2DM 患者（8 例男性），病史>5 年，三联口服抗糖尿病药物治疗失败，目前正在使用胰岛素（≥0.7 U/kg/天）至少 1 年，谷氨酸脱羧酶抗体阴性。纳入的患者正在服用过去 3 个月稳定剂量的药物。主要终点是自体骨髓源性干细胞移植（SCT）后 6 个月时胰岛素需求减少≥50%，以及胰高血糖素刺激 C 肽水平改善，次要终点是与基线相比体重、HbA1c 和血脂水平的变化。与基线相比，7 例患者对治疗有反应，胰岛素需求减少了 75%。达到主要目标的平均时间为 48 天。虽然有 1 例患者的胰岛素停药时间很短，但 3 例患者能够完全停用胰岛素。HbA1c 平均降低 1%，7 例应答者中有 3 例 HbA1c 值<7%。应答者体重显著减轻 5.5kg，而非应答者体重增加 2.2kg。然而，体重减轻与胰岛素需求减少无关（r=0.68，P=0.06）。整个组和应答者的空腹和胰高血糖素刺激 C 肽水平均显著改善（P=0.03）。整个组的 HOMA-B 显著增加（P=0.02）和应答者（P=0.04），而 HOMA-IR 没有显著变化（P=0.74）。胰岛素剂量减少与基线时刺激 C 肽反应相关（r=0.83，P=0.047）和输注干细胞的单核细胞计数相关（r=0.57，P=0.04）。未观察到严重不良事件。我们的观察结果表明，SCT 是一种安全有效的治疗方法，可改善 T2DM 患者的β细胞功能。然而，需要进一步的大规模研究来证实这些观察结果。
